The cognizance that an infectious disease can be caused by many variants of a particular infectious agent/pathogen prevalent in diverse geographical regions of the globe has resulted in a paradigm shift in regards to development of efficacious vaccine, diagnostic and therapeutic measures against such pathogens. In particular, the focus has shifted from modalities that narrowly target one particular pathogen variant (strain) that predominates in a specific geographical area to those that broadly cover all pathogen strains with disease causing potential in different parts of the globe. This paradigm shift has brought with it a set of unique challenges, especially those that pertain to the identification of pathogen components, including proteins that are “shared” by all of the variants. Because such “shared” or “conserved” proteins have potential to be the basis for development of broad management options against infectious diseases, the formulation of strategies that facilitate definition of shared/conserved pathogen proteomes (the complement of proteins encoded by the pathogen genome) is of high priority.
In this context, one approach for defining such pathogen protein components is to zero in on those that are produced by the pathogen (and its variants) when it is engaged in an actual process of infection of the host (in vivo expressed or WE). The rationale is that a subset of WE proteins confers on the pathogen the ability to cause disease, and hence these WE proteins are likely to have excellent vaccine, diagnostic and therapeutic potential. Historically, a popular strategy for identification of IVE pathogen proteins has been to exploit the defense (also called the immune response, characterized by production of diverse host molecules, including antibodies) mounted by a host in response to an infection caused by a particular pathogen. This strategy is predicated on the premise that antibodies are produced against infection-relevant pathogen proteins, and hence are an apt tool for identifying IVE proteins using well-established protocols.
Despite this, antibodies produced by a host during natural infection/disease are limited and not ideal for identification of “shared/conserved” pathogen proteins. The vast majority of these “shared” proteins (or “shared” regions or “epitopes” [regions on proteins that are the actual targets of antibodies] on disparate proteins) are involved in functions that are indispensable to the pathogen, as a consequence of which they have remained unchanged (conserved) through evolution. Given their importance, pathogens have developed multiple “decoy” mechanisms, which are deployed during natural infection/disease, to either “hide” these “shared/conserved” epitopes from the host immune response (FIG. 1, Panel I) or prevent access of antibodies generated against these highly conserved proteins from reaching their cognate targets by antibodies against those pathogen epitopes/proteins that are produced by only some of the variants i.e., strain-specific and not shared/conserved (FIG. 1, Panel II; antibodies against strain-specific proteins induce excellent protection against disease with the same strain but not related strains).